Scientists successfully combine antibody-drug conjugates with immunotherapy

Researchers from the University of Basel have, for the first time, successfully combined an antibody-drug conjugate with a therapy that stimulates the immune system to attack breast cancer cells.

This opens the door to new therapeutic options in the treatment of breast cancer.

In nearly every fifth breast cancer patient, an above-average number of HER2 receptors are located on the surface of the tumour cells. The overabundance of receptors causes the cancer cells to divide rapidly and the tumour grows faster than average.

For some years now, a new class of drugs called antibody-drug conjugates have been used, which work in two ways: they consist of an antibody that binds selectively to the tumour cell receptor and interrupts the signal to propagate; they also act as a transport vehicle for a chemical substance that enters the cancer cells with the antibody and triggers their death.

Researchers, led by Prof. Alfred Zippelius at the Department of Biomedicine, from the University and University Hospital Basel have now gone one step further: in a preclinical study performed in mouse breast cancer models, they combined the antibody-drug conjugate ‘trastuzumab emtansine’ with an additional immunotherapy that activates the immune system into attacking tumours more efficiently.

Antibody-drug conjugate combination therapy led to a complete cure in some mice

They focused on immunoregulatory checkpoints. These are receptors on immune cells, which control for example effector T-cells by dampening their activation if damage to healthy cells is imminent. By administering a complementary antibody, they blocked the function of two such immune checkpoints, whereby different types of endogenous T-cells were activated.

On its own, this immune response had no immediate effect in the fight against the utilised breast tumours, but in combination with the antibody-drug conjugate it proved itself effective in attacking cancer cells in mice, resulting in the complete cure of the majority of mice receiving the combination therapy. The researchers were also able to further demonstrate that regulatory T-cells play a host protective role in this therapeutic setting. Their removal resulted in excessive inflammation and tissue damage.